5 Insulin Secretion And Intermediary Metabolism Flashcards
Q: What 4 hormones cause glucose levels to rise?
A: glucagon
catecholamine
somatotrophin (growth hormone)
cortisol
Q: When comparing high and low blood glucose, what can our body manage for a period of time? What does the alternative cause?
A: high
other is life threatening as brain needs glucose to function (therefore body needs methods of maintaining plasma glucose levels)
Q: What is type 1 diabetes mellitus defined as?
A: elated glucose where insulin is required to prevent ketoacidosis
not enough insulin is produced
Q: What is ketoacidosis? Can cause?
A: ketoacidosis, the body fails to adequately regulate ketone production causing such a severe accumulation of keto acids that the pH of the blood is substantially decreased
can cause damage to big blood vessels in brain/heart (causing stroke/heart attack)
Q: What is type 2 diabetes mellitus defined in terms of?
A: glucose but also related to hypertension and dyslipidaemia
hyperglycaemia
Q: Put in order of prevalence; T1DM, T2DM, MODY.
A: T2DM (85%)
T1DM (11%)
MODY (4%)
Q: What is the role of diet in treating DM T1 and 2?
A: 1- counting carbohydrates is essential in controlling sugar levels
2- suggested that sufferers have a healthy diet (control calories and fats and refined sugars)
Q: As part of DM treatment insulin can be given and its attempted to do so physiologically. Why is this hard?
A: recreating what occurs in a patient is difficult
w/o diabetes, the body makes insulin on a moment to moment basis depending on food intake, aa, glucose
Q: Describe glucose monitoring. (3)
A: in the past- measured urine glucose
capillary glucose measuring needs to be done frequently
some patients measure interstitial space glucose (not same as blood glucose) with permanent/semi indwelling monitors
Q: The imbalance of what causes hypoglycaemia? (3)
A: diet, exercise, insulin
Q: When is hypoglycaemia inevitable?
A: if you have T1DM (low blood sugar)
Q: Name 4 complications of diabetes mellitus.
A: Diabetic retinopathy
Nephropathy
Heart attacks
Stroke
Q: Why is glucose so important?
A: Glucose is a very important energy substrate, particularly for the CNS which mainly respires glucose under normal conditions- can use ketones (not fats at all)
Q: What occurs if blood glucose falls below 4.0-5.5mM?
A: hypoglycaemia- then brain function is increasingly impaired
Q: What occurs if blood glucose falls below 2mM? What do most people have?
A: it could lead to unconsciousness, coma and death
have a counter regulatory system that deals w/ low blood sugar (eg alpha cells and glucagon)
Q: What is 98% of the pancreas associated with? And the remaining 2%?
A: exocrine secretions via a duct to the small intestine (involved in digestion)
are islets of Langerhans (small clumps of cells within pancreatic tissue)- endocrine secretions (hormone straight into blood stream)
Q: What is the structure of the islets of Langerhans? Include diagram.
A: made of 3 cell types; alpha (make glucagon), beta (make insulin), delta
have gap junctions- allow small molecules to pass directly between cells
have tight junctions- form small intercellular spaces between them= have high hormone concentration
Q: What do the cell types of the islets of Langerhans produce? (3) What do these molecules do?
A: Alpha= Glucagon= increases blood glucose
Beta= Insulin= stimulates growth and development and decreases blood glucose
Delta= Somatostatin= important in hormone balance since it decreases production of insulin and glucagon
Q: What factors affect beta cells and their insulin production? Increase? (4) Decrease? (2)
A: increase
increased blood glucose (MAIN)
certain aa
certain gastrointestinal hormones
parasympathetic activity
decrease
somatostatin from delta cells sympathetic activity (alpha receptors)- needs stimulus
Q: What does increased insulin do? (3)
A: decrease lipolysis + increase lipgenesis (fat storage)
increase aa transport +
increase protein synthesis
increase gluconeogenesis +
increase glycolysis +
increase glucose transport into cells via GLUT4 -> decease blood glucose
Q: What is the neurological control of beta cells? (2)
A: Sympathetic Stimulation - switches off insulin to increase blood glucose concentration
Parasympathetic Stimulation - increases insulin secretion
Q: What factors affect alpha cells and their glucagon production? Increase? (5) Decrease? (2)
A: increase
decreased blood glucose (MAIN) certain aa certain gastrointestinal hormones sympathetic activity parasympathetic activity
decrease
insulin from beta cells
somatostatin from delta cells
Q: What does increased glucagon do? (3) Overall.
A: increase lipolysis-> increased gluconeogenesis
increase hepatic glycogenolysis
increase aa transport into liver -> increased gluconeogenesis
all 3 -> increased blood glucose
Q: How does low blood glucose treatment giving differ from home and hospital?
A: home- injection of glucagon (if they’re asleep)
hospital- if unconscious -> intravenous glucose
Q: What is glucokinase, how does it work (3) and why is it important? Known as? (2)
A: Glucokinase is the Rate Determining Step that regulates insulin secretion
known as glucose sensor and hexokinase IV
- Glucose enters the beta islet cell via Glucose Transporter 2 (Glut 2) which is not insulin sensitive (NOT INSULIN REGULATED)
- Glucose is converted to Glucose-6-phosphate by glucokinase which is important for the sensing of glucose concentration by the beta cell
- metabolic pathways -> insulin synthesis and release
Q: What is the structure of insulin? How is it formed?
A: Insulin is constructed as pre-proinsulin which has three chains forming one long chain along with a signal sequence
The C peptide is then removed
Insulin being released by the pancreas is always released with C peptide
The molar ratio of insulin to C peptide is 1:1 so by measuring C peptide you can measure endogenous insulin production and see if the beta cells are functioning
Q: Why is insulin given as an injection rather than orally?
A: would be broken down and made inactive if taken orally
Q: Illustrate the production of insulin by beta cells. (5)
A: Glucose enters through Glut 2
converted to glucose 6 phosphate -> makes ATP
The ATP produced blocks the ATP sensitive potassium channels
This leads to the opening of voltage dependent calcium channels (membrane potential has changed)
Calcium rushes into the beta cell and stored insulin is secreted and new insulin made
Q: What could mean that those with T2 diabetes can make enough insulin?
A: if glucose exposure was prolonged (since they can’t produce enough insulin at once to deal with the meal)
Q: What is the incretin effect? Include experiment.
A: When we eat a meal and there is food in our intestine we start producing insulin
In this experiment someone is given a 50g oral glucose load and a matched intravenous infusion of glucose to cause exactly the same glucose profile
When given oral glucose, he makes considerably more insulin - this is the incretin effect
Incretin Effect - food stimulates more insulin secretion if given orally rather than intravenously
Q: Describe glucagon like peptide-1 (GLP-1). What is it? When is it secreted? How? What does it stimulate and affect? (3) Half life?
A: Gut hormone
Secreted in response to nutrients in the gut
It is a transcription product of the proglucagon gene - mostly from the L cell
Stimulates insulin and suppresses glucagon
Increases satiety (increases feeling of fullness)
They have a short half life due to rapid degradation by the enzyme Dipeptidyl Peptidase-4 (DPPG-4)
Q: Illustrate first phase insulin release on a diagram. 2 lines. Why is it important? Get around by?
A: 1. The normal person has an intravenous glucose load which makes him produce a lot of insulin instantly
- The person with T2DM has next to no first phase insulin - the insulin is made later on (no insulin store available)
If someone has an oral glucose load you don’t see the first phase because it’s over 30 mins
First phase insulin release is important is important in switching off liver glucose production
can get round physiological process by prolonging calorie exposure- give patients meals that give calories over 2/3 hours and not a high glucose meal
Q: Illustrate the insulin receptor. (4)
A: 2 alpha subunits= extracellular domains (insulin above)
membrane
beta subunits with tyrosine kinase domains
^ (autophosphorylation and cross-phosphorylation of receptors)
-phosphorylation of cell protein substrates
Q: How do abnormalities in the insulin receptor cause T1 and 2 DM?
A: they don’t
Insulin resistance lies in the post receptor cytoplasmic elements of insulin function
Q: What occurs when insulin binds to its receptor? (2) Effects? (4) What’s important and why?
A: The alpha subunit of the insulin receptor recognises the 3D shape of insulin
which causes a conformational change in the beta subunits which cross the membrane
- this has a metabolic effect on glucose,
- amino acids
- and fatty acids
- It also affect growth (mitogenic pathway)
Phosphorylation of beta subunits is important in recruiting substrates which go on to have effects on the metabolic pathway
